The comprehensive understanding and proper use of supramolecular interactions have become critical for the development of functional materials, and so is the biomedical application of nucleic acids (NAs). Relatively rare attention has been paid to hydrophobic interaction compared with hydrogen bonding and electrostatic interaction of NAs. However, hydrophobic interaction shows some unique properties, such as high tunability for application interest, minimal effect on NA functionality, and sensitivity to external stimuli. Therefore, the widespread use of hydrophobic interaction has promoted the evolution of NA‐based biomaterials in higher‐order self‐assembly, drug/gene‐delivery systems, and stimuli‐responsive systems. Herein, the recent progress of NA‐based biomaterials whose fabrications or properties are highly determined by hydrophobic interactions is summarized. 1) The hydrophobic interaction of NA itself comes from the accumulation of base‐stacking forces, by which the NAs with certain base compositions and chain lengths show properties similar to thermal‐responsive polymers. 2) In conjugation with hydrophobic molecules, NA amphiphiles show interesting self‐assembly structures with unique properties in many new biosensing and therapeutic strategies. 3) The working‐mechanisms of some NA‐based complex materials are also dependent on hydrophobic interactions. Moreover, in recent attempts, NA amphiphiles have been applied in organizing macroscopic self‐assembly of DNA origami and controlling the cell–cell interactions.

中文翻译：

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疏水相互作用：核酸生物医学应用的有前景的驱动力。

全面理解和正确利用超分子相互作用对于功能材料的开发至关重要，核酸（NA）的生物医学应用也是如此。与 NA 的氢键和静电相互作用相比，疏水相互作用相对较少受到关注。然而，疏水相互作用显示出一些独特的性质，例如应用兴趣的高度可调性、对 NA 功能的影响最小以及对外部刺激的敏感性。因此，疏水相互作用的广泛使用促进了基于NA的生物材料在高阶自组装、药物/基因递送系统和刺激响应系统中的进化。本文总结了基于 NA 的生物材料的最新进展，其制造或性能很大程度上取决于疏水相互作用。1）NA本身的疏水相互作用来自碱基堆积力的积累，通过这种积累力，具有一定碱基组成和链长的NA表现出类似于热响应聚合物的性能。2) NA 两亲物与疏水分子结合，在许多新的生物传感和治疗策略中表现出有趣的自组装结构，具有独特的性质。3）一些基于NA的复合材料的工作机制也依赖于疏水相互作用。此外，在最近的尝试中，NA两亲物已被应用于组织DNA折纸的宏观自组装和控制细胞与细胞的相互作用。